2. Academic Validation
  3. Overcoming the Blood-Brain Tumor Barrier with Docetaxel-Loaded Mesoporous Silica Nanoparticles for Treatment of Temozolomide-Resistant Glioblastoma

Overcoming the Blood-Brain Tumor Barrier with Docetaxel-Loaded Mesoporous Silica Nanoparticles for Treatment of Temozolomide-Resistant Glioblastoma

  • ACS Appl Mater Interfaces. 2024 May 1;16(17):21722-21735. doi: 10.1021/acsami.4c04289.
Tsung-I Hsu 1 2,  Yi-Ping Chen 3 4,  Rong-Lin Zhang 5,  Zih-An Chen 3,  Cheng-Hsun Wu 5,  Wen-Chang Chang 6,  Chung-Yuan Mou 5 7,  Hardy Wai-Hong Chan 5,  Si-Han Wu 3 4
Affiliations

Affiliations

  • 1 Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei 110, Taiwan.
  • 2 International Master Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
  • 3 Graduate Institute of Nanomedicine and Medical Engineering, Taipei Medical University, Taipei 110, Taiwan.
  • 4 International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.
  • 5 Nano Targeting & Therapy Biopharma Inc., Taipei 110, Taiwan.
  • 6 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  • 7 Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
PMID: 38629735 DOI: 10.1021/acsami.4c04289
Abstract

While temozolomide (TMZ) has been a cornerstone in the treatment of newly diagnosed glioblastoma (GBM), a significant challenge has been the emergence of resistance to TMZ, which compromises its clinical benefits. Additionally, the nonspecificity of TMZ can lead to detrimental side effects. Although TMZ is capable of penetrating the blood-brain barrier (BBB), our research addresses the need for targeted therapy to circumvent resistance mechanisms and reduce off-target effects. This study introduces the use of PEGylated mesoporous silica nanoparticles (MSN) with octyl group modifications (C8-MSN) as a nanocarrier system for the delivery of docetaxel (DTX), providing a novel approach for treating TMZ-resistant GBM. Our findings reveal that C8-MSN is biocompatible in vitro, and DTX@C8-MSN shows no hemolytic activity at therapeutic concentrations, maintaining efficacy against GBM cells. Crucially, in vivo imaging demonstrates preferential accumulation of C8-MSN within the tumor region, suggesting enhanced permeability across the blood-brain tumor barrier (BBTB). When administered to orthotopic glioma mouse models, DTX@C8-MSN notably prolongs survival by over 50%, significantly reduces tumor volume, and decreases side effects compared to free DTX, indicating a targeted and effective approach to treatment. The apoptotic pathways activated by DTX@C8-MSN, evidenced by the increased levels of cleaved Caspase-3 and PARP, point to a potent therapeutic mechanism. Collectively, the results advocate DTX@C8-MSN as a promising candidate for targeted therapy in TMZ-resistant GBM, optimizing drug delivery and bioavailability to overcome current therapeutic limitations.

Keywords

blood−brain tumor barrier; docetaxel; glioblastoma; mesoporous silica nanoparticles; temozolomide resistant.

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